Hindawi Publishing Corporation

ISRN Gastroenterology
Volume 2014, Article ID 619628, 5 pages
http://dx.doi.org/10.1155/2014/619628

Research Article
Comparison of Laboratory Data of Acute Cholangitis Patients
Treated with or without Immunosuppressive Drugs
Minoru Tomizawa,1 Fuminobu Shinozaki,2 Rumiko Hasegawa,3
Yoshinori Shirai,3 Noboru Ichiki,3 Yasufumi Motoyoshi,4 Takao Sugiyama,5
Shigenori Yamamoto,6 and Makoto Sueishi5
1

Department of Gastroenterology, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
2
Department of Radiology, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
3
Department of Surgery, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
4
Department of Neurology, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
5
Department of Rheumatology, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
6
Department of Pediatrics, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City,
Chiba 284-0003, Japan
Correspondence should be addressed to Minoru Tomizawa; nihminor-cib@umin.ac.jp
Received 8 January 2014; Accepted 5 March 2014; Published 10 March 2014
Academic Editors: A. J. Karayiannakis, A. Mencarelli, and L. Rodrigo
Copyright 2014 Minoru Tomizawa et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Objective. Symptoms and laboratory data between acute cholangitis (AC) patients treated with and AC patients treated without
immunosuppressive drugs (corticosteroids or methotrexate) were compared to identify factors that can be meaningful to the
diagnosis of AC. Methods. The Wilcoxon signed-rank test was used for comparison of baseline variables between the patients with
AC treated with immunosuppressive drugs and those without it. The chi-squared test was used in the analysis of the symptoms.
Results. In total, 69 patients with AC were enrolled. Fifteen patients were treated with immunosuppressants due to rheumatoid
arthritis or other collagen diseases. Jaundice was less frequent in the patients treated with immunosuppressive drugs ( = 0.0351).
T-Bil level was marginally lower in the patients treated with immunosuppressants ( = 0.086). AST and ALT levels were lower in
the patients treated with immunosuppressants ( = 0.0417 and 0.022, respectively). Conclusions. The frequency of jaundice and
AST and ALT levels were lower in the patients treated with immunosuppressive drugs. It is recommended that care be taken to
evaluate jaundice, AST level, and ALT level in the diagnosis of AC.

1. Introduction
Acute cholangitis (AC) is a bacterial infection caused by
obstruction of the bile duct [13]. AC should be treated
promptly because it can be fatal owing to sepsis [4, 5].
Biliary drainage is performed by endoscopic retrograde
cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography, or endoscopy-guided ultrasonography

[6]. The prompt and accurate diagnosis of AC is a necessity.

The diagnosis of AC is based on the presence of inflammation
and biliary obstruction [7, 8]. Laboratory data are indispensable for the diagnosis of AC. These include the following:
white blood cell (WBC) count and C-reactive protein (CRP),
total bilirubin (T-Bil), alkaline phosphatase (ALP), aspartate
aminotransferase (AST), alanine aminotransferase (ALT),
and gamma-glutamyl transpeptidase (-GTP) levels [6, 9].

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Some AC patients are simultaneously being treated for a
collagen disease such as rheumatoid arthritis [10]. Collagen
diseases are treated with immunosuppressive drugs that
consist of corticosteroids, methotrexate (MTX), and, recently,
biological agents such as etanercept. Corticosteroids include
prednisolone and methylprednisolone. AST and ALT levels
increase subsequent to the administration of a combination
of corticosteroids and other immunosuppressive drugs [11].
The distribution of changes is not different between immunosuppressants. MTX antagonizes folate and inhibits DNA
synthesis. It is also associated with hepatotoxicity [12]. Etanercept antagonizes tumor necrosis factor- and suppresses
the immune system [13]. This agent is also associated with
hepatotoxicity [14]. Hepatotoxicity can potentially interfere
with the correct diagnosis of AC. The alteration of WBC
count and T-Bil levels may result in a failure to correctly
assess the severity of AC [15]. A comparison of laboratory
data between the AC patients treated with and those treated
without immunosuppressive drugs is, however, not available.
We therefore compared laboratory data between AC
patients treated with and AC patients treated without
immunosuppressive drugs.

2. Materials and Methods

2.1. Inclusion Criteria. Patient records from April 2008 to
March 2013 were retrospectively analyzed. Our study was
subjected to approval by our institutional ethical committee
and determined not to be a clinical trial since it was performed as part of daily clinical practice. Written informed
consent was obtained for each session of ERCP. Written
informed consent to undergo contrast-enhanced computed
tomography (CECT) or magnetic resonance cholangiopancreatography (MRCP) was also obtained from the patients.
Patient anonymity was preserved.

ISRN Gastroenterology
2.4. Endoscopic Retrograde Cholangiopancreatography. ERCP
procedures were performed by experienced endoscopists
with JF-260V video duodenoscopes (Olympus, Tokyo,
Japan). Papillotomies were performed with a pull-type
sphincterotome (Boston Scientific, Natick, MA). Stones or
sludge were removed with a basket or balloon catheter. If
necessary, a nasobiliary catheter was inserted for drainage.
2.5. Imaging Diagnostics. Patients with suspected AC underwent CECT and abdominal ultrasound to further investigate
biliary dilatation, common bile duct stones, and cancer. From
May 2012, the patients underwent MRCP using a 1.5-Tesla
scanner (Achieva, software version 3.2.2, Philips Medical
Systems, Best, The Netherlands). Before May 2012, some
of the patients were referred to Sannou Hospital (Chiba
City, Japan) for MRCP. CECT was performed using a 16detector row CT scanner (SOMATOM Emotion 16, Siemens,
Munich, Germany). The contrast medium was administered
intravenously as follows: 100 mL of iopamidol at 3 mL/s
(Konica Minolta Healthcare, Tokyo, Japan). CT images were
acquired before the injection of contrast medium, and 30,
70, and 180 s later. Abdominal ultrasound was performed
with an SSA-700A instrument (Toshiba Medical Systems
Corporation, Ohtawara, Japan) by senior fellows of the
Japan Society of Ultrasonics in Medicine, using a 5.0 MHz
curved-array transcutaneous probe or an 8.0 MHz lineararray transcutaneous probe.
2.6. Statistical Analysis. The Wilcoxon signed-rank test was
used for comparison of baseline variables between the AC
patients treated with and those treated without immunosuppressive drugs. The chi-square test was used in the analysis of
the symptoms and severity of AC.

3. Results
2.2. Immunosuppressive Drugs. The immunosuppressants
used included prednisolone, methylprednisolone, and MTX.
Biological agents such as etanercept were also included.
2.3. Diagnostic Criteria for Acute Cholangitis. The patients
were diagnosed with AC when they showed fever, abdominal
pain, and jaundice (Charcots triad). If a patient did not show
all the components of Charcots triad, AC was diagnosed
in the presence of an inflammatory response and biliary
obstruction. An inflammatory response consisted of fever,
elevation of WBC count, or elevation of C-reactive protein
level. Biliary obstruction consisted of bile duct dilatation, biliary stricture, a common bile duct stone, ALP level elevation,
or -GTP level elevation. The severity of AC was assessed
according to the Tokyo Guidelines (TG13) [8]. Patients were
considered to have severe AC when they showed at least one
of the following: cardiovascular, neurological, respiratory,
renal, hepatic, or hematological dysfunction. Moderate AC
was defined as the presence of at least 2 of the following
abnormalities: abnormal WBC count, high fever, high T-Bil
level, and hypoalbuminemia.

In total, 69 patients with AC were enrolled. Thirty-seven

were male (mean SD age, 69.5 8.3 years), and 32
were female (mean SD age, 68.2 12.3 years). AC was
caused by bile duct stones in 66 cases, bile duct cancer in
2 cases, and pancreatic cancer in 1 case. Eight patients were
treated with a corticosteroid, and 4 were treated with MTX
(Table 1). Three patients were treated with a combination of a
corticosteroid and MTX. Fourteen patients were treated with
immunosuppressive drugs for rheumatoid arthritis.
Symptoms are important for the diagnosis of AC. Symptoms were compared between the patients who were treated
with immunosuppressive drugs and those who were not.
Table 2 shows a comparison of the number of patients with
abdominal pain, fever, and jaundice in each group. The
number of patients with jaundice was significantly lower
among those treated with immunosuppressive drugs ( =
0.0351).
Blood examination results were also compared between
the 2 groups of patients (Table 3). The WBC count was
marginally higher in the patients treated with immunosuppressive drugs than in those who were not. AST and ALT

ISRN Gastroenterology

3
Table 1: Patients characteristics.

Number
Age, years
Cause of acute cholangitis
Bile duct stone
Bile duct cancer
Pancreatic cancer
Immunosuppressant
()
Corticosteroid
Methotrexate
Corticosteroid + methotrexate
Immunosuppressant indication
Rheumatoid arthritis
Microscopic polyangitis
Polyarteritis nodosa
Polymyalgia rheumatica

Male
37
69.5 8.4

Female
32
65.3 12.3

Total
69
67.5 10.5

35
2
0

31
0
1

66
2
1

33
1
2
1

21
7
2
2

54
8a,b
4c
3

3
1
0
0

11
0
1
1

14
1
1
1

One female with methylprednisolone, and the other patients with prednisolone; b one female with prednisolone and etanercept; c one female with methotrexate
and etanercept.

Table 2: Comparison of symptoms.

Abdominal pain ( = 0.6315)
()
(+)
Immunosuppressant
()
(+)
Total

18
6
24

36
9
45

Total

54
15
69

Fever ( = 0.6293)
()
(+)
29
7
36

25
8
33

Total

54
15
69

Jaundice ( = 0.0351)
()
(+)
23
11
34

31
4
35

Total

54
15
69

The values indicate the statistical significance according to the chi-square test.

Table 3: Comparison of patient baseline variables.

WBC
CRP
T-Bil
ALP
AST
ALT
-GTP

Immunosuppressant ()
Average
95% CI
8,802
7,47310,130
4.96
2.937.00
2.50
1.613.39
661
537784
182
117247
200
147254
380
287473

Immunosuppressant (+)
Average
95% CI
11,506
8,98514,027
6.74
2.9210.56
2.24
0.553.93
629
399859
176
53300
148
45252
339
165512

value
0.0735
0.9646
0.0860
0.6249
0.0417
0.0220
0.3395

WBC: white blood cell; CRP: C-reactive protein; T-Bil: total bilirubin; ALP: alkaline phosphatase; AST: aspartate aminotransferase; ALT: alanine
aminotransferase; -GTP: gamma-glutamyl transpeptidase; CI: confidence interval.

levels were significantly lower in the patients treated with

immunosuppressants.
Finally, the severity of AC was compared between the 2
patient groups (Table 4). The percentage of mild, moderate,
or severe AC did not differ significantly between the 2 groups.

4. Discussion
Overall, no significant differences in laboratory data were
observed between the patients treated with and those treated
without immunosuppressive drugs. Abdominal pain is omitted from the TG13, but the symptom is still important [8].

ISRN Gastroenterology
Table 4: Comparison of acute cholangitis severity.

Mild
Immunosuppressant
()
(+)
Total

44
12
56

Severity ( = 0.9694)
Moderate
6
2
8

Severe
4
1
5

Total

54
15
69

The values indicate the statistical significance according to the chi-square test.

Fever is an indicator of inflammation. Our study shows that

the presence of both symptoms is similar between the AC
patients treated with and those treated without immunosuppressive drugs. This suggests that the diagnosis of AC can be
expected to be made with similar accuracy in both patient
groups.
Jaundice is a component symptom in Charcots triad. In
our study, the frequency of jaundice was lower in the patients
treated with immunosuppressants. T-Bil level was marginally
lower in the patients treated with immunosuppressive drugs.
Consistent with our results, corticosteroids were shown to
reduce T-Bil in patients with biliary atresia [16]. This report
and our data suggest that immunosuppressive drugs decrease
T-Bil levels. However, the mechanism of this reduction is not
known. With regard to AC, it is recommended that jaundice
and T-Bil level be carefully evaluated during diagnosis.
Unexpectedly, AST and ALT levels were lower in the
patients treated with immunosuppressive drugs. These were
expected to be higher in the patients treated with immunosuppressive agents because they potentially cause hepatotoxicity. The reason is not known. It is speculated that the mechanism of hepatotoxicity differs between immunosuppressant
drugs and biliary obstruction. Drug-related hepatotoxicity
comprises drug-induced liver injury and is associated with
apoptosis [17]. Conversely, bile duct obstruction causes damage to hepatocyte membranes via bile acids, accumulated
copper, and membrane peroxidation [18, 19].
One might expect that immunosuppressive agents could
be applied to AC patients to reduce the damage of liver
caused by obstructive jaundice. The patients should be treated
with ERCP and the other intervention [6]. The elevated liver
damage would be decreased.
In conclusion, it is recommended that care be taken to
avoid underestimating AST and ALT levels for the diagnosis
of AC according to the TG13 [8].

5. Conclusions
The frequency of jaundice and AST and ALT levels were lower
in the patients treated with immunosuppressive drugs. It is
recommended that care be taken to evaluate jaundice and
AST and ALT levels in the diagnosis of AC.

Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.

Acknowledgments
The authors thank the Department of Radiology, Sannou
Hospital, for performing MRCP. The authors also thank the
Department of Radiology, National Hospital Organization
Shimoshizu Hospital, for performing all the radiological
examinations.

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